Continuous sharing of users’ location information is vital for decision-making applications, such as smart health care, smart traffic analysis, etc. Since this data originates from users’ private information, protecting their privacy is crucial. Local Differential Privacy is a modified version of standard differential privacy that enables users to anony mize their location data before transmission to service providers or applications, thus safeguarding users’ privacy even in the presence of hostile service providers. However, The LDP approach offers strong privacy protection against threats or attacks by assuming that a user’s location data points are independent of one another. But in fact, the location data points of a user may be correlated, which increases privacy risks because traditional LDP does not provide enough privacy budget for these correlated data points in order to gain strict privacy. To address this challenge, our paper proposes a approach for distributing a adequate budget to correlated data points and proving that our approach achieves LDP across an infinite user location stream. Our proposed met hod comprises two phases: first, computing dissimilarity between current and previous published location information, and second, based on the dissimilarity computed in the first phase, the method makes a decision on whether to publish the current location data point or a null publication. Finally, we tested our method using real and simulated datasets, and the results show that it guarantees LDP privacy for users, regardless of whether their location data points are correlated. And also improves data utility as compared with existing methods.

Natural woodland expansion into old-field sites is valuable for nature conservation and international commitments to expanding forests. However, successful colonisation of trees and long-term woodland health depend on interactions with established vegetation, land use history, and suitable microclimatic conditions. Understanding the effect of these factors is crucial for anticipating woodland expansion outcomes, given the long periods and large scales involved. We used a novel combination of airborne photogrammetry and field measurements to evaluate the key determinants of long-term success of Juniperus thurifera in a 20 km² region of central Spain. A canopy height model, trained on field-measured biomass, was used to map juniper stand biomass, and time-series of land-cover were used to estimate the age of regenerating woodland patches. These datasets allowed us to evaluate the drivers of variable success in natural colonisation using a space-for-time substitution within the expansion frontier. Dramatic land cover shifts have occurred over the last 34 years, including a 75 % reduction in agricultural land and a tripling of open woodland. Juniper woodland has expanded out from steep slopes onto flatter land, and into sites with less extreme irradiance. Increasing dwarf shrubland density within stands significantly reduced juniper biomass by up to 25 % in the oldest woodlands. Higher insolation was associated with faster biomass accumulation over time but lower biomass in new woodlands. New stands with low insolation showed greater biomass stocks for their age compared to old stands, indicating potential benefits from land use legacies in the absence of drought stress. Our findings show substantial juniper woodland expansion over the last 34 years, indicating different constraints on growth at the expanding front. Using field methods and high-resolution photogrammetry, we highlight the importance of local competition and abiotic conditions for expanding growth over large spatial scales and multi-decadal time scales.

Within the framework of a random network, where the network architecture specifies the directional flow between nodes, this study delves into the SIR (Susceptible-Infected-Recovered) model. We incorporate two distinct time delays into the model: one representing the recovery period of infected individuals and the other the incubation time for susceptibles to become infectious. The model is developed using continuous-time and discrete-space equations that account for dual delays within the diffusion network. By employing the delay as a bifurcation parameter, we derive the essential conditions for the onset of Hopf bifurcation. The stability of this Hopf bifurcation is then scrutinized utilizing the central manifold theory. Our numerical simulations confirm that the stability features associated with the Hopf bifurcation can trigger disease outbreaks. Furthermore, our research reveals that the connection probability within the network significantly alters the spatio-temporal dynamics of the epidemic spread. This insight underscores the importance of network connectivity in influencing epidemic patterns and has implications for public health interventions and disease control strategies.

Geostress, the stress within the Earth’s crust, is a critical factor in subsurface systems, yet its direct measurement is challenging and often prohibitively costly. This study develops a mathematical framework to model geostress distribution trends under quasi-static conditions using finite element methods (FEM). Leveraging known surface deformation, subsurface horizon deformation, and fault geometry—readily obtainable via InSAR, 3D seismic interpretation, or other geophysical techniques—we derive a model based on gravitational loading and gravity-derived prestress, yielding a standardized trend for underground horizon geostress distribution. Mathematical derivations address regional variations in material properties, anisotropy, layer attributes, and fault parameters, enhancing the framework’s theoretical flexibility. Dynamic factors, such as tectonic events and injection-induced seismicity, challenge this static model, exposing its limitations and raising significant mathematical questions for future theoretical exploration. These findings establish a robust foundation for advancing geostress analysis, offering insights into subsurface stress modeling through rigorous mathematical methods.

Linear solvers and eigensolvers are the heart of HPC scientific applications. Among them, iterative projection methods are preferred to direct algorithms for large problems because of their lower memory usage, but they are prone to roundoff errors. Using an enhanced working precision inside the linear computing kernels mitigates this issue and accelerates convergence. Today, to go beyond 80 bits of precision, the only option is to use software libraries which are very slow. We introduce the VaRiable and extended Precision Accelerator (VRP), a RISC-V accelerator implemented on a System-on-Chip (SoC) using GF22FDX technology. The VRP supports Floating Point (FP) computations with a range of significand bits from 2 to 512. This accelerator delivers an average 19.25x application speedup compared to the well-known MPFR software library running on a 2400 MHz Intel Xeon processor. Additionally, extended precision facilitates the convergence of linear solvers for problems that would otherwise fail to converge and reduces energy-to-solution.

Objective: Our study aims to explore the effect of neuromuscular electrical stimulation on diastasis recti abdominis. Design: This is a 1:1 paired prospective study Setting: This study conducted at Fujian Maternity and Child Health Hospital Population or Sample: This study recruited 78 women who were in early postpartum period Methods: The control group received health education and intervention group received neuromuscular electrical stimulation Main Outcome Measures: Transabdominal ultrasound was used to measure the inter-recti distance of three points (2-3cm above, at, and 2-3cm below the umbilicus) Results: Post-intervention, the control group exhibited reduced IRD only at the umbilicus ( P<.001), whereas the intervention group showed significant reductions at all three points ( P<.001, P<.001, P=.005, respectively). Compared to the control group, the inter-recti distance of 2-3cm above and umbilicus were lower in the intervention group ( P=.026 and P=0.046), the differences remained significant after adjusting covariates at three points ( P=.001, P<.001, and P<.001, respectively) Conclusions: Neuromuscular electrical stimulation significantly accelerates diastasis recti abdominis recovery in the early postpartum period, demonstrating clinical potential as a non-invasive therapeutic option

Damage Control Laparotomy and Evacuation of Hemoperitoneum Resulting in Stabilization of Coagulopathy in Amniotic Fluid Embolism Todd Lovgren Niyati Nadkarni Nebraska Methodist Health System, Omaha Nebraska, USA

Objectives: The NLRP3 inflammasome-mediated pyroptosis in gingival fibroblasts (GFs) has been implicated in the pathogenesis of periodontitis. Mitochondrial dysfunction represents a critical upstream event in NLRP3 inflammasome activation, while mitophagy functions as an essential cellular mechanism for maintaining mitochondrial homeostasis. Therefore, the present study was designed to elucidate the regulatory role and molecular mechanisms of mitophagy in modulating pyroptosis in GFs. Materials and methods: Human GFs were used in this study. An in vitro inflammatory environment was established using 5 μg/ml lipopolysaccharide (LPS). GFs exposed to LPS were treated with 10 μM P62-mediated mitophagy inducer (PMI), while healthy GFs not exposed to LPS received 10 μM Mdivi-1 intervention. Mitophagy was visualized by immunofluorescence, and the expression levels of PINK1, Parkin, and Beclin-1 were assessed via qRT-PCR and Western blot. Mitochondrial morphology was examined by Transmission electron microscopy (TEM), and mitochondrial damage was evaluated through measurements of mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS) levels using flow cytometry. NLRP3 inflammasome activation was analyzed by qRT-PCR and Western blot. Propidium iodide (PI) staining, lactate dehydrogenase (LDH) release, IL-1β and IL-18 expression levels and apoptosis assays were also detected to assess pyroptosis in GFs. Results: LPS stimulation suppressed mitophagy in GFs, which was reversed by mitophagy activator. In contrast, mitophagy inhibition decreased basal mitophagy in healthy GFs. Mitophagy activation maintained mitochondrial function by enhancing MMP and reducing ROS/mtROS accumulation and mtDNA/nDNA ratio in LPS-stimulated GFs. Furthermore, mitophagy attenuated LPS-induced NLRP3 inflammasome activation and decreased GF death, and IL-1β/IL-18 production and secretion. Conclusions: Mitophagy alleviates NLRP3 inflammasome-dependent pyroptosis of GFs by maintaining mitochondrial homeostasis.

Title PageTitle: Comment on: Enoxaparin thromboprophylaxis in hospitalized obese pediatric patientsArticle type: Letter to the EditorCorrespondence: 1. Saifullah KhanEmail: Saifullah.Khan23@dmc.duhs.edu.pkInstitute: Dow University Of health sciencesAddress: SMCHS Block A, Karachi, PakistanORCID: 0009-0008-6278-9971Co-authors: 2. Maria BaigEmail: Maria.Baig23@dmc.duhs.edu.pkORCID: 0009-0001-5077-9839Institution: Dow University Of Health SciencesWord count: 470Conflict of interest: noneDeclaration: noneAcknowledgments: noneFunding: none

A good number of studies were performed on the fatigue characterization of natural rubbers (NR) filled with Caron Nanotubes (CNTs). However, less attempts were given to: (i) understand how dispersion techniques employed in compounding CNTs/NR can affect the dynamic properties of NR as each dispersion approach can lead to different microstructural characteristics in terms of state of CNT dispersion and pores, (ii) have deep grasping of damage evolution in CNTs/NR nanocomposites at macro and micro scales. Therefore, this study was aimed to investigate the fatigue life of CNTs filled natural rubbers prepared by two different compounding techniques including wet and dry methods. This was done to correlate the presence of defects to fatigue performance and to find out the optimum dispersion approach for CNTs/NR compounding. The wet approach possessed higher number of large defects compared to the dry approach whereas the latter method manifested better CNT dispersion. The presence of a higher number of large defects including voids were accounted for a significant reduction of the fatigue life in the wet batch with respect to dry samples. Formation of multiple tiny cracks and their further developments via crack-shielding and crack-coalescence were considered for damage evolution at the macro-scale while the presence of wrenching, resulting from Strain Induced Crystallization (SIC), and river-like patterns on fracture surfaces were notable at the micro-scale. It was concluded that the dry approach could be a better compounding technique for the CNT dispersion considering its high quasi-static and fatigue properties, less environmental concerns thanks to no usage of solvent and cost effectiveness.

Background: While pegylated E. Coli asparaginase (PEG) is an integral component of leukemia and lymphoma treatment, hypersensitivity reactions (HSR) remain a common adverse event, often resulting in adjustments to the treatment regimen, increasing the burden on patients and families. HSR to asparaginase often indicates a transition to Erwinia asparaginase (ERW), which requires patients to return to the hospital six times for subcutaneous injections to replace one dose of IV PEG. Previous trials have demonstrated rates of HSR to pegylated E coli asparaginase (PEG) anywhere from 0.5% to 25%. At our institution, despite premedication with antihistamine medications such as diphenhydramine and famotidine, we have observed a similar range of patients develop treatment-limiting HSR to PEG. Additionally, nonallergic infusion reactions (IR) often overlap symptomatically with HSR, making it difficult to identify true HSR, thus leading to the conservative clinical decision to remove asparaginase from the treatment plan. There are reports of adding hydrocortisone to the premedication regimen for patients receiving PEG, but this has been reported mainly in the rechallenge setting. Methods: We conducted a retrospective analysis evaluating the benefits of adding hydrocortisone to a universal two-drug premedication regimen of famotidine and diphenhydramine. Data was gathered via chart audit comparing a group of patients with a 2-drug regimen (diphenhydramine and famotidine) to a group of patients with a three-drug regimen of diphenhydramine, famotidine, and hydrocortisone. Analysis included patients with any lymphoid malignancy treated with a frontline PEG-containing treatment regimen. A one-year time interval was used to collect data for the pre- and post-intervention groups. All patients who received IV PEG were reviewed. HSRs or infusion reactions were reviewed independently to confirm and grade using Common Terminology Criteria for Adverse Events (CTCAE), v5 of allergic reactions. Results: In 86 patients analyzed over a 2-year period, 51 were in Group 1 and given a 2-drug regimen of diphenhydramine and famotidine prior to PEG infusion. The rate of HSR in group 1 was 37.3% with 11.8% experiencing IRs. Group 2 contained 35 patients who received a 3-drug regimen with diphenhydramine, famotidine, and hydrocortisone. The rate of HSR in group 2 was 11.4% with another 11.4% experiencing IRs. Based on this data, rates of IR remained unchanged, while rates of HSR decreased significantly by more than 25% (p-value 0.0079) with the addition of hydrocortisone to the pre-medication regimen. Conclusions: Our retrospective cohort study provided preliminary evidence that the addition of hydrocortisone to a two-drug premedication regimen of diphenhydramine and famotidine can decrease the rates of hypersensitivity reactions to IV PEG.

| The article presents a simple and universal method for preparation of cross-sectional TEM specimens from semiconductor heterostructures using ion milling in broad-beam Ar + ions. The implemented original ideas concern some modification of standard equipment or the way it is used. We studied the relief transformation of specimens containing a thin layer of epoxy resin during ion milling and the dependence of the relief pattern on two parameters, namely the displacement of the gluing line and ion beams relative to the axis of specimen rotation. Based on experimental results, a rationale was given for the preferable use of a single-sector ion milling, as well as milling in “counter ion beams”. Using this method, sufficiently wide and uniform electron transparent areas of foils on multilayer heterostructures containing both soft (InP, InAlAs) and hard (GaN, Al 2O 3) materials were obtained with minimal effects of preferential sputtering and redeposition.

Populism has long accompanied the development of modern democracies like a shadow, reflecting the presence of institutional faults. Given populism’s discursive targeting of elites, it is particularly attractive to those who feel unfairly treated by the current state of affairs. In this paper, we look at how these populist grievances change in reaction to electoral events. Specifically, we assess perceptions of fairness and apply them to an electoral context. To accomplish this, we conducted a longitudinal study of three time-points throughout the 2024 US presidential election (n = 540), two before and one after the election. We hypothesised that changes in perceptions of electoral fairness, particularly among partisans whose candidate lost, would meaningfully affect an individual’s populist attitudes post-election. Using mediation analyses, we found that decreases in both electoral fairness evaluations and democratic satisfaction mediated an increase in populist attitudes only among Democrats, while serial mediation revealed a causal link between electoral fairness and democratic satisfaction. Although democratic satisfaction may represent a broader attitude towards electoral systems, perceptions of unfairness within the electoral process also have the potential to stoke populist sentiment. We discuss the mechanics of this effect and other procedural contexts which may be of further interest.

The aftermath of the 2024 elections highlighted Latine voters’ increasingly pivotal influence on American politics, as their record-high, pro-Republican support helped Donald Trump cinch the presidency. While many were surprised by this political shift, we propose that historically contextualizing Latines’ political allegiances can illuminate the motivated, social identification process that underlie them. We argue that Latines’ individual differences in racial phenotypicality and power motives influence the plausibility and desirability of strong, politically consequential, psychological ties to their ethnic (i.e., Latine) and national (i.e., American) group memberships. In Study 1 (N= 3,753 Latines), using a large, post-election survey, we show that bearing greater physical resemblance to a prototypical (i.e., White, non-Hispanic) American indirectly predicts pro-Republican support in 2020 via greater feelings of inclusion in U.S. society and greater prioritization of American (vs. Latine) identity. In Study 2 (N= 493 Latines), analyses show that racial phenotypicality (i.e., looking like the prototypical “American” vs. looking like the prototypical “Latino”) moderates the indirect relationship between power motives and pro-Republican support in the 2024 election via feelings of similarity with, and positive attachment to, the American group.

Situated in the tropical rain forests of the Riviera Maya, bounded to the south by the biodiverse Sian Ka'an preserve, our team embarked on the design of Casa Oleaje using principles from the fields of bioengineering and architecture. During the design process, we incorporated engineering techniques to create a holistic environment which encourages recovery and neurological flow states. Additionally, the timeless architectural style creates a space to separate the occupant from the currents of modernity. We believe the lessons learned during the design can be adopted by other buildings to achieve the same benefits.

Since cocoa seed fermentation is a spontaneous and uncontrolled process, it is mediated by a complex microbial consortium that significantly affects the quality of the final product. Given that Hanseniaspora spp. has been identified as a dominant genus during the fermentation process and that efficient microorganisms are required for use in starter cultures, this study aimed to analyze the genomes of Hanseniaspora spp. obtained from metagenomic shotgun sequencing of cocoa bean fermentation samples from the Ilhéus/BA region. The genomes of Hanseniaspora spp. were assembled using SPAdes, and gene ontologies (GO) were determined using OmicsBox, EggNOG, and REVIGO. The main biological activities identified in the genes encoded by Hanseniaspora spp. revealed mechanisms associated with biogenesis, as well as the metabolism of carbohydrates, aromatic compounds, glycoproteins, and organic acids, among others. These metabolic activities directly influence the production of volatile organic compounds, which contribute to the development of a diverse range of aromatic flavor molecules. The functional annotation performed indicates that Hanseniaspora spp. possesses a highly compatible metabolic profile suited for the fermentation process, suggesting its potential use as a starter inoculum.

Created in response to an environmental disaster, GRIIDC has always focused efforts on gaining trust with users. After the Deepwater Horizon oil spill in 2011, GRIIDC was tasked with rapidly developing a data repository for researchers funded by the Gulf of Mexico Research Initiative (GoMRI) who were currently conducting studies and had never shared data before. The repository also had to cater to multiple disciplines, given the broad environmental and sociological effects of the spill. Although researchers were mandated to share their data, enforcement was a challenge requiring time and effort. GRIIDC has learned to gain user trust by continuous communication through one-on-one support, training and workshops, and participation in conferences. GRIIDC also offers helpful services that address every step of the data management life cycle: planning, organizing, submitting, curating, and distributing. The dataset monitoring page allows data submitters, managers, and funding agencies the ability to track the status of a dataset throughout the GRIIDC data package review process. Following TRUST and FAIR principles, GRIIDC collects detailed metadata that includes standardized keywords, data use license, spatial extent, point of contact, parameters and units, among other information. Dataset landing pages contain information to help a user decide if they want to download the data, including methods, file format, point of contact in case a user has questions, and any associated publications. A suggested citation is provided to encourage proper credit of the author, instilling trust in the data sharing process and alleviating concerns about theft. Data are also curated to ensure they are properly documented with detailed metadata and are in non-proprietary formats that will be useful in the future. Providing easy to use submission and planning tools and multiple opportunities for training helps build and keep trust with users. Serving the 10-year GoMRI program has established a track record with users who are familiar with the GRIIDC system and are more willing to share data from other funded projects with GRIIDC. GRIIDC continues to prioritize user needs and develop features that follow FAIR and TRUST principles.

Demi-plié is a coordinated ballet movement involving a smooth, continuous bend of the knees, keeping the thighs externally rotated and heels on the ground. It consists of descending and ascending phases, the latter often preparing for the next motor action. Task goals may influence corresponding brain activation patterns. Twelve classical dancers (10 females, 2 males) performed the demi-plié itself and prior to other ballet movements such as: relevé; sauté; sissonne fermée de côté; and pirouette en dehors. Electroencephalography measures were taken from the primary motor area (M1), premotor cortex (PMC), and supplementary motor area (SMA) during the movement performance. Significant differences were found among the demi-plié in preparation for complex movements such as jumps and turns. Wavelet spectrograms showed distinct patterns of brain activation for all experimental conditions. Additionally, the M1, PMC, and SMA seem to display different orders of activation depending on the demi-plié end-goal.

The paraventricular nucleus of the thalamus (PVT) is a central node in brain networks controlling motivated behaviors. It processes inputs from cerebral cortex, brainstem and hypothalamus and has efferents that project to a wide range of structures, including the nucleus accumbens (nAcc). It is known that PVT neurons projecting to the nAcc show c-Fos activation in response to reward-related cues, in well trained animals. We previously found that c-Fos expression is also increased early in the conditioning process, during the first session of learning a new cue-reward association in rats, but neurons with projections to nAcc were not identified in that study. Here we tested the hypothesis that nAcc-projecting PVT neurons would show this enhanced c-Fos expression following first exposure to the association of a visual cue with a subsequent food reward. Male rats were stereotaxically injected in the nAcc with a retrogradely transported adeno-associated virus construct leading to green fluorescent protein (GFP) expression in cell bodies of afferents from PVT. Following a single session of cue-reward training, processing of the brains with dual immunohistochemistry for c-Fos and GFP showed significantly higher density of double labelled neurons in the conditioned group, compared to controls in which the same number of cues and rewards were delivered at random intervals with respect to each other. Such activation of immediate early gene expression in PVT to nAcc projecting neurons very early in paired associative reward learning may have a role in modulating plasticity in the nAcc.

By: Fatima Shaikh

Background: Polycystic ovarian disease is the most prevalent endocrine ailment that affects a woman’s hormones, menstrual cycle, fertility, and physical appearance among women age group of 14-35 years. Teenagers who have poor eating habits and little exercise are more likely to develop disorders like polycystic ovarian disease (PCOD). Objectives: The aim of this study to assess the knowledge regarding PCOD and to evaluate the effectiveness of planned teaching programme regarding PCOD among high school girls. Materials and Methods: Quantitative evaluative research approach was used in this study. The research design was Pre-experimental one -group pre-test, post-test research design. The study was conducted at CKS High school Hassan, Karnataka. A total 100 high school students were willing to participate in the study. Main outcome measures to see the effective to improve the knowledge among high school girls. Results: Among 100 students (69%) of the respondents had adequate knowledge, 31% of them had moderate knowledge regarding poly-cystic ovarian disease. The mean knowledge score 19.07± 4.0 and 32.80±2.73. The Calculated paired‘t’ test value was 42.35 (p<0.05, df= 99), Conclusion: The researcher concluded that the planned teaching programme was more effective. The findings of the study suggest that the adolescent girl were having less on PCOD, So Obstetrics and Gynecological nurses, nurse educators and researchers play a vital role in both prevention of infertility and development of better management technique to encounter the problems in adolescent girls with PCOD.

Objective: The increased risk of antepartum stillbirth in mothers of Late Maternal Age (≥35 years of age) is well known. We sought to determine if this has changed over time. Design: Retrospective cohort study. Setting: The Canadian province of Alberta 1992-2019. Sample: All singleton births ≥23 weeks of gestation comprising 1,202,659 births with 3,749 antepartum stillbirths. Methods: Maternal age was categorized as <20, 20-34, 35-39 and ≥40 years of age and multivariate logistic regression analysis was performed. The fetus at risk approach was used to examine the risk of stillbirth by gestational age. An estimate of the optimal gestational age for delivery was calculated with a perinatal index. Year of birth was categorized by 1992-94, 1995-99, 2000-04, 2005-09, 2010-14, and 2015-19. Main outcome measures: Antepartum stillbirth, intrapartum stillbirth and neonatal death. Results: Compared to the baseline group of 20–34-year-old mothers, on adjusted analysis, both maternal age groups of 35-39 and ≥40 years were associated with antepartum stillbirth, odds ratio, 1.35; 95% confidence interval (1.23, 1.49) and odds ratio, 1.98; 95% confidence interval (1.67, 2.30). Over the study period we observed a decline in the rate for the 35–39-year-old age group from 5.1/1000 to 2.86/1000 and 5.1/1000 to 3.39/1000 for the ≥40-year-old group. Post dates delivery declined in both groups. Conclusions: Late maternal ae is independently associated with antepartum stillbirth. The risk has decreased over the study period due to a deliberate policy of earlier delivery at term.

Background: In atrial fibrillation (AF) patients, breakthrough stroke is not uncommon and represents an important subgroup due to its high stroke recurrence rate and mortality. However, no reliable tool exists for assessing stroke risk in anticoagulated paroxysmal AF (PAF) patients. While LOXL2 is implicated in atrial fibrosis, a key pathological substrate for atrial thrombus, its predictive value for stroke remains unclear. Objective: To investigate predictive value of serum LOXL2 levels for breakthrough stroke risk in PAF patients. Methods: We consecutively enrolled 197 anticoagulated PAF patients. The serum level of LOXL2 were quantified via ELISA. Patients were stratified into LOXL2+ and LOXL2− groups based on the median of their baseline LOXL2 (275.9 pg/mL). Stroke events were recorded over a median follow-up of 3.9 years. Predictive models incorporating LOXL2, age, and CHA2DS2-VASc were evaluated using ROC, NRI, and DCA. Results：During follow-up, 24 patients (12.2%) experienced stroke. LOXL2 levels were significantly higher in stroke cases (P = 0.006). Multivariable Cox analysis identified LOXL2 as an independent risk factor (P < 0.001). Kaplan-Meier and Nelson-Aalen cumulative hazard analyses further confirmed the contribution of LOXL2 for elevated stroke risk. A prediction model, incorporating both LOXL2 and age, achieved the highest predictive accuracy (AUC = 0.842), significantly improving risk stratification over CHA2DS2-VASc (NRI = 15.0%, P < 0.001). Conclusion: Elevated LOXL2 is independently associated with breakthrough stroke risk in PAF patients. Incorporating LOXL2 and age enhances predictive accuracy, offering a novel tool for personalized stroke risk stratification in AF patients despite anticoagulation medication.

Introduction: The pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) remains mysterious and specific predictive markers are lacking. This study aimed to elucidate the molecular underpinnings and identify predictive biomarkers of DEACMP through multi-omics and single-nucleus RNA sequencing (snRNA-seq). Method: We collected clinical data and blood samples from 105 participants. Untargeted metabolomics sequencing was employed to profile serum metabolites across these participants. Additionally, individuals from the healthy controls (HCs), acute carbon monoxide poisoning patients (ACOP), non-delayed encephalopathy after ACOP (DEACMP-N), and DEACMP groups (n=3 each) were randomly selected for transcriptome sequencing to identify potential predictive targets and pivotal signaling pathways associated with DEACMP. Furthermore, we established severe DEACMP and Control rat models, three rats from the Control, DEACMP, and DEACMP + Dexamethasone + Selenomethionine groups were selected for snRNA-seq. Immunofluorescence multiplexing and qRT-PCR were then performed to validate the identified predictive targets. Results: Our analysis of clinical data from 105 participants highlights the pivotal role of inflammation in influencing the prognosis of carbon monoxide poisoning. Metabolomics analysis identified 19 metabolites that significantly differed between the DEACMP-N and DEACMP groups. Transcriptomics analysis of 12 participants indicated that DEACMP is primarily associated with six signaling pathways, including lysosome and tuberculosis. Given that microglia are central nervous system immune effectors, our snRNA-seq analysis revealed altered genes expression and signaling pathways in microglia during DEACMP, with KEGG analysis highlighting neutrophil extracellular trap formation, lysosome, and tuberculosis as the predominant pathways. Differential gene analysis from transcriptome and snRNA-seq identified 28 genes differentially expressed in DEACMP. The STRING database, immunomultiplexing and qRT-PCR confirmed the pivotal role of the Ifngr1/Stat1/Ctss axis in DEACMP. Conclusion: This study provides a comprehensive overview of serum metabolite expression, differential genes expression, and signaling pathways in DEACMP, offering a theoretical foundation for understanding the pathogenesis for DEACMP.